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Mooderal

Posted in Health Care

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Feel Joy and Excitement Again with Mooderal Neurotransmitter Support System

  • Anti-depressive
  • Anti-anxiety
  • Improved sleep
  • Reduced mental fatigue
  • Synergistic effects with 5-HTP and L-Tyrosine
  • Effective doses of each substance
  • Developed by Swedish doctors and scientists

Scientific background to Mooderal

The monoamines serotonin, dopamine and noradrenaline have a great impact on mood, emotion and behaviour. It is suggested that monoaminergic systems are involved in several psychiatric disorders such as depression, psychosis, ADHD and anxiety. The psychologist Silvan Tomkins has identified eight basic emotions.[1] According to Tomkins there are two positive emotions Interest/excitement and enjoyment/joy, one neutral: Surprise/startle, and five negative: Distress/anguish, fear/terror, shame/humiliation, contempt/disgust and anger/rage. The Swedish doctor and researcher Hugo Lövheim has recently combined the knowledge about the monoaminergic system with the eight basic emotions [2], and illustrated this in the so-called Lövheim’s cube, figure 1.

Emotion Cube

Figure 1: Lövheim’s "emotion cube".
NE = Norepinephrine (or noradrenaline)
DA = Dopamine
5-HT = 5-Hydroxytryptamine (or serotonin)

From this cube we can conclude that if there are low brain levels of all three neurotransmitters the person will experience the feeling of shame and humiliation. If we then selectively increase the amount of serotonin, contempt and disgust will be experienced, unless the dopamine levels are increase simultaneously. If dopamine and serotonin levels are kept elevated, a feeling of joy will be present. To excitement to occur a slight increased level of noradrenaline is required as well. Thus, to move the negative mood state into joy and excitement, a delicate and optimal amount of neurotransmitters must be present.

All these neurotransmitters are synthesised from amino acids (which are provided from the diet):

L-Phenylalanine ––> L-Tyrosine ––> L-Dopa ––> Dopamine ––> Noradrenaline

And;

L-Tryptophan ––> 5-Hydroxytryptophan (5-HTP) ––> Serotonin

The most popular antidepressent drugs (SSRI) increase the amount of serotonin between brain neurones (by inhibiting the re-uptake in the synaptic cleft). This is a rather slow process. Normally it takes several weeks before the patient experience improved mood. Furthermore, the treatment is not effective in all patients. Sometimes these patients get better results from using medications that also increase the amount of noradrenaline (by so called SNRI-drugs). This emphasise the importance of a proper balance between the different neurotransmitters.

mooderal-supplement-facts

5-HTP

Several clinical trials have concluded that by providing 5-HTP as a dietary supplement, the mood can be improved.{3-5] A review identified 11 double-blind, placebo controlled studies, of which 7 showed an effect above placebo6. This may not sound impressive, unless one realise that this proportion of positive studies is the same as for antidepressive drugs (about 50%). There is also plenty of empirical data showing the effectiveness of this treatment. Many times the patient feels better after a few days of treatment. This rapid improvement has also been demonstrated in a recent study of 70 depressive patients. After 8 weeks the effect from 5-HTP and fluoxetine (a common SSRI-drug) was considered as equal, but at 2 weeks only the group receiving 5-HTP had improved.[7] Studies comparing 5-HTP to imipramine (an antidepressive drug) could not notice any difference in effectiveness between the two treatments.[8]

There are also several human studies, including one study in children, indicating that 5-HTP is effective against anxiety and panic attacks.[8-10] Patients frequently report a feeling of joy and calm during 5-HTP treament, but rarely do they report increased activity level, or excitement. Studies even indicate that monotherapy with 5-HTP may impairs decision making11-12, suggesting an anti dopamine action12. Interestingly, it has been noted that isolated supplementation of 5-HTP may deplete or reduce the bioactivity of catecholamines such as dopamine [13-15] and that this relationship also acts in reverse, with supplemental L-Tyrosine possibly able to deplete 5-HTP and serotonin itself [16]. When dopamine depletion is great enough, 5-HTP administration will no longer function [17], making mono therapy with 5-HTP contraindicated. Some researchers have therefore suggested that combination therapy of 5-HTP and L-Tyrosine could be a useful avenue for anti-depressive effects.[18]

L-Tyrosine

Although the effects of L-Tyrosine on human depression have not been systematically investigated, a number of facts do indicate an important role. In animals, feeding L-Tyrosine can attenuate the development of behavioural abnormalities associated with acute uncontrollable stressors19-20, which otherwise depletes noradrenaline stores.[19,20] Likewise, one study in humans subjected to high altitudes has noted protective effects from L-Tyrosine against acute stress symptoms. Less headaches, stress, fatigue, distress, sleepiness, muscular soreness, and coldness were observed (assessed by the Environmental Symptoms Questionnaire). This study also noted improvements (relative to placebo) on global ratings of mood and happiness (assessed by Clyde Mood Scale and Profile of Mood states) and cognitive function21. Similar results are noted with the same oral dose after acute noise stressor.[22] One study in children with diagnosed ADHD given a combination supplement of L-Tyrosine and 5-HTP23 showed good results. However, in this study also other supplements were given, which may have confounded the result. In most human studies the dose given was about 5-10 g daily. At this dose, L-Tyrosine will likely deplete the levels of 5-HTP and serotonin [16-17], thus being counter-productive against depression. Therefore, for the indication of depression, and in combination with 5-HTP, a lower dose of L-Tyrosine is recommended.

Enzyme inhibition

In perhaps the most successful 5-HTP study, involving therapy resistant depressive patients, the participants were also given carbidopa24, a drug that inhibits the peripheral conversion from 5-HTP to serotonin, by inhibiting AAD (Aromatic amino acid decarboxylase). Since 5-HTP, but not serotonin, can pass the blood-brain barrier, inhibition of the peripheral conversion will increase the amount of 5-HTP that can reach the brain, to be converted into active serotonin.

Aromatic L-amino acid decarboxylase (a k a dopamine decarboxylase) is expressed in stomach tissue and liver. Inhibition of this enzyme in the stomach during 5-HTP ingestion promote the concentration of 5-HTP that reaches neural tissue, which is supported by a study using carbidopa (pharmaceutical inhibitor) alongside 5-HTP to increase radioactivity of 5-HTP (indicative of neural accumulation) in humans.[25] Pretreatment with decarboxylase inhibitors before 5-HTP administration may increase plasma levels of 5-HTP 10 times26. At the same time, some rather common side effects of 5-HTP like nausea, vomiting and diarrhoea may be reduced with decarboxylase inhibition.[27]

In regard to brain catecholamine metabolism, L-dopa, dopamine and noradrenaline are inactivated (and finally excreted) by methylation and deamination by COMT and MAO, respectively.Green tea catechins, especially the epicatechin EGCG, irreversibly inhibit ADD28, and thus decrease the amount of peripheral serotonin. EGCG also preserves brain dopamine levels during stress and inflammation, probably due to inhibiting the COMT-enzyme.[29,30] Finally, green tea catechins may inhibit both MAO-A and MAO-B activity.[31,32]

 

In summary, administration of green tea epicathecins is a natural way to optimise the enzymatic activities that control mood and well-being.

 

B-Vitamins

Vitamin B6 (pyridoxine) is an important cofactor factor for ADD33. B6 deficient rats will produce very little serotonin34 In experiments with monkeys and rats, the presence of ample amounts of B6 - even to the point of ”moderate excess” - increased production of serotonin in the brain from 5-HTP by up to 60%.[35,36] Low levels if Vitamin B12 (cobalamin) in serum has been linked to depression.[37 High B12 levels are, on the other hand, associated with good response to anti-depressant treatment.[37-38]

Conclusion

By co-ingesting 5-HTP and L-Tyrosine with a high potency green tea extract and B-vitamins, enzyme activities in the monoaminergic systems will be optimised and neurotransmitter levels normalised. In this way, Mooderal will help elevate your mood and wellbeing.

 

References

1. Tomkins S. Affect theory. In: Ekman P, Friesen W, Ellsworth P, editors. Emotions in the human face. Cambridge: Cambridge University Press; 1982.p. 355–95.

2. Lövheim H. A new three-dimensional model for emotions and monoamine neurotransmitters. Med Hypotheses. 2012 Feb;78(2):341-8.

3. van Praag et al. A pilot study of the predictive value of the probenecid test in application of 5-hydroxytryptophan as antidepressant. Psychopharmacologia 1972, 25, 14-21.

4. van Praag, H. M., & de Haan, S. (1981). Chemoprophylaxis of depressions. An attempt to compare lithium with 5-hydroxytryptophan. Acta Psychiatr Scand Suppl 290, 191– 201.

5.Quadbeck et al. Comparison of the antidepressant action of tryptophan, tryptophan/5-hydroxytryptophan combination and nomifensine. Neuropsychobiology 1984,11,111–115.

6. Turner EH et al. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 2006 Mar;109(3):325-38. Review.

7. Jangid P et al. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. 2013 Feb;6(1):29-34.

8. Angst J et al. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr. 1977 Oct 11;224(2):175-86.

9. Schruers K et al. Acute L-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients. Psychiatry Res. 2002 Dec 30;113(3):237-43.

10. Maron E et al. The effect of 5-hydroxytryptophan on cholecystokinin-4-induced panic attacks in healthy volunteers. J Psychopharmacol. 2004 Jun;18(2):194-9 11. Bruni O et al. L -5-Hydroxytryptophan treatment of sleep terrors in children. Eur J Pediatr. 2004 Jul;163(7):402-7.

11. Gendle MH & Golding AC. Oral administration of 5-hydroxytryptophan (5-HTP) impairs decision making under ambiguity but not under risk: evidence from the Iowa Gambling Task. Hum Psychopharmacol. 2010 Aug;25(6):491-9

12. Gendle MH, Young EL, Romano AC. Effects of oral 5-hydroxytryptophan on a standardized planning task: insight into possible dopamine/serotonin interactions in the forebrain. Hum Psychopharmacol. 2013 May;28(3):270-3.

13. Zhelyaskov DK et al. Tryptophan derivatives as inhibitors of tyrosine hydroxylase in vivo and in vitro. Mol Pharmacol. 1968;4(5):445–451.

14. Ng LKY et al. Release of [3H] dopamine by L-5-hydroxytryptophan. Brain Research. 1972;45(2):499–505.

15. Stamford JA et al. Striatal dopamine terminals release serotonin after 5-HTP pretreatment: in vivo voltammetric data. Brain Res. 1990;515(1–2):173–180.

16. Breier JM et al. L-tyrosine contributes to (+)-3,4-methylenedioxymethamphetamine-induced serotonin depletions. J Neurosci. 2006;26(1):290–299.

17. Hinz M et al. 5-HTP efficacy and contraindications. Neuropsychiatr Dis Treat. 2012;8:323-8

18. Gelenberg AJ & Gibson CJ. Tyrosine for the treatment of depression. Nutr Health. 1984;3(3):163-73.

19. Lehnert H et al. Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine. Brain Res. 1984 Jun 15;303(2):215-23. Rauch TM el al Lieberman HR.

20 Rauch TM el al Lieberman HR. Tyrosine pretreatment reverses hypothermia-induced behavioral depression. Brain Res Bull. 1990 Jan;24(1):147-50.

21. Banderet LE & Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull. 1989 Apr;22(4):759-62.

22. Deijen JB & Orlebeke JF. Effect of tyrosine on cognitive function and blood pressure under stress. Brain Res Bull. 1994;33(3):319-23.

23. Hinz M et al. Treatment of attention deficit hyperactivity disorder with monoamine amino acid precursors and organic cation transporter assay interpretation. Neuropsychiatr Dis Treat. 2011;7:31–38.

24. Zmilacher K et al. L-5-hydroxytryptophan alone and in combination with a peripheral decarboxylase inhibitor in the treatment of depression. Neuropsychobiology. 1988;20(1):28-35.

25. Orlefors H et al. Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography. Eur J Nucl Med Mol Imaging. 2006 Jan;33(1):60-5.

26. Magnussen I & Engbaek F. The effects of aromatic amino acid decarboxylase inhibitors on plasma concentrations of 5-hydroxytryptophan in man. Acta Pharmacol Toxicol (Copenh). 1978 Jul;43(1):36-42.

27. Byerley WF et al. 5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects. J Clin Psychopharmacol 1987;7(3):127-137.

28. Bertoldi M et al. Green tea polyphenols: novel irreversible inhibitors of dopa decarboxylase. Biochem Biophys Res Commun. 2001 Jun 1;284(1):90-3.

29.Chen D et al. Inhibition of human liver catechol-O-methyltransferase by tea catechins and their metabolites: structure-activity relationship and molecular-modeling studies. Biochem Pharmacol. 2005 May 15;69(10):1523-31.

30. Chen WQ et al. Effects of epigallocatechin-3-gallate on behavioral impairments induced by psychological stress in rats. Exp Biol Med (Maywood). 2010 May;235(5):577-83.

31. Bandaruk Y et al. Evaluation of the inhibitory effects of quercetin-related flavonoids and tea catechins on the monoamine oxidase-A reaction in mouse brain mitochondria. J Agric Food Chem. 2012 Oct 17;60(41)

32. Lin SM et al. Protective effect of green tea (-)-epigallocatechin-3-gallate against the monoamine oxidase B enzyme activity increase in adult rat brains. Nutrition. 2010 Nov-Dec;26(11-12):1195-200.

33. Shabbir F et al. Effect of diet on serotonergic neurotransmission in depression. Neurochem Int. 2013 Feb;62(3):324-9. doi: 10.1016/j.neuint.2012.12.014. Epub 2013 Jan 7.

34. Dakshinamurti K et al. Nonparallel changes, in brain monoamines of pyridoxine deficient growing rats. Exp Brain Res. 1976;26:355-366.

35.Hartvig P, Lindner KJ, Bjurling P, Langstrom B, Tedroff J. Pyridoxine effect on synthesis rate of serotonin in the monkey brain measured with positron emission tomography. J Neural Trans 1995;102:91-97.

36.Dakshinamurti K, Sharma SK, Bonke D. Influence of B vitamins on binding properties of serotonin receptors in the CNS of rats. Klin Wochenschr 1990;68:142-145.

37. Syed EU et al. Vitamin B12 supplementation in treating major depressive disorder: a randomized controlled trial. Open Neurol J. 2013 Nov 15;7:44-8.

38. Hintikka J et al. High vitamin B12 level and good treatment outcome may be associated in major depressivedisorder. BMC Psychiatry. 2003;3:17–22

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